title: Ultralow concentrations of bupivacaine exert anti-inflammatory effects on inflammation-reactive astrocytes.
abstract: Bupivacaine is a widely used, local anesthetic agent that blocks voltage-gated Na(+) channels when used for neuro-axial blockades. Much lower concentrations of bupivacaine than in normal clinical use, < 10(-8)  m, evoked Ca(2+) transients in astrocytes from rat cerebral cortex, that were inositol trisphosphate receptor-dependent. We investigated whether bupivacaine exerts an influence on the Ca(2+) signaling and interleukin-1β (IL-1β) secretion in inflammation-reactive astrocytes when used at ultralow concentrations, < 10(-8)  m. Furthermore, we wanted to determine if bupivacaine interacts with the opioid-, 5-hydroxytryptamine- (5-HT) and glutamate-receptor systems. With respect to the μ-opioid- and 5-HT-receptor systems, bupivacaine restored the inflammation-reactive astrocytes to their normal non-inflammatory levels. With respect to the glutamate-receptor system, bupivacaine, in combination with an ultralow concentration of the μ-opioid receptor antagonist naloxone and μ-opioid receptor agonists, restored the inflammation-reactive astrocytes to their normal non-inflammatory levels. Ultralow concentrations of bupivacaine attenuated the inflammation-induced upregulation of IL-1β secretion. The results indicate that bupivacaine interacts with the opioid-, 5-HT- and glutamate-receptor systems by affecting Ca(2+) signaling and IL-1β release in inflammation-reactive astrocytes. These results suggest that bupivacaine may be used at ultralow concentrations as an anti-inflammatory drug, either alone or in combination with opioid agonists and ultralow concentrations of an opioid antagonist.
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Linda
authors.initials: L
authors.lastname: Block
authors.forename: Per
authors.initials: P
authors.lastname: Jörneberg
authors.forename: Ulrika
authors.initials: U
authors.lastname: Björklund
authors.forename: Anna
authors.initials: A
authors.lastname: Westerlund
authors.forename: Björn
authors.initials: B
authors.lastname: Biber
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Hansson
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D002045:Bupivacaine / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000098:blood supply / Q000166:cytology; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D053583:Interleukin-1beta; D017470:Receptors, Glutamate; D017450:Receptors, Opioid, mu; D011985:Receptors, Serotonin; D002118:Calcium; D002045:Bupivacaine
keywords: 5-HT; astrocytes; bupivacaine; glutamate; opioids; rat